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The world of medicine has a new turning point before it: the long-awaited magic bullet against obesity is almost here. After a century of searching for that holy grail, drugs based on mimicking glucagon-like peptide-1 are yielding the first results.

GLP-1 analogues, although more famous by their trade names Ozempic and Wegovy, are set to erase one of the pandemics of the 37st century: obesity and its most immediate effects, such as diabetes and cardiovascular problems. In Spain alone, according to the Global Obesity Observatory, 8.16% of adults weigh more than recommended and <>% are obese.

"There is a lot of science behind these drugs," says Cristóbal Morales, a member of the Board of Directors of the Spanish Society of Obesity (Seedo). "We are in a new era in obesity control, there are more than 150 clinical trials. It's a revolution of new molecules," he adds.

More than 1 years have passed since the first description of GLP-40 in an article in the Proceedings of the National Academy of Sciences to the current results. This long-awaited search has not only given way to drugs that control type 2 diabetes and make people lose weight, but they have also become best-selling drugs capable of dealing with the disease and also what causes it: a poor diet, that is, the processed industry.

Antidiabetic drugs. Chronology

"The weight losses are significant and with each new drug it is greater. It goes from 8% to 15%," says Morales. Which in kilos translates into decreases of more than 12 kilos in some patients.

But let's take it one step at a time. What is the secret of LPG-1s? "The compound in Ozempic (semaglutide) is a molecule that we already have in our body, but modified so that it takes longer to degrade and therefore can be used as a drug: it is GLP-1, which is secreted in the intestine and sends signals to the brain and the rest of the digestive tract, indicating that food has already arrived and that you don't need to eat any more," explains Francisco Tinahones, researcher at CIBEROBN, Scientific Director of IBIMA and head of Endocrinology and Nutrition at the Virgen de la Victoria University Hospital (Málaga). And he adds that "it is an anorexigenic molecule, which takes away the appetite and also relaxes the stomach, so you have the feeling of being full when eating food".

It reduces hunger and satisfies, two key actions when you want to avoid excessive intake. Olga González, head of the Endocrinology Service at the Gregorio Marañón Hospital in Madrid, offers more details: "At the stomach level, gastric emptying slows down. It slows down the passage to the digestive tract and intestine when you eat a meal, which provides a feeling of fullness. This is a very potent mechanism in the first few weeks of treatment, then it goes down."

In addition, Gonzalez discusses the other powerful mechanism: its ability to act on the satiety centers in the brain. "The drug is able to cross the blood-brain barrier, reach the central nervous system and act on the satiety and appetite centers, although the intrinsic pathways by which the drug removes hunger are not known."

Antidiabetic drugs. Mechanism

However, let's not forget that these drugs were first invented to combat diabetes and that the weight loss observed in studies and throughout their use could be considered a positive side effect.

Clotilde Vázquez, head of the Department of Endocrinology and Nutrition at the Jiménez Díaz Foundation in Madrid, recalls that "when the first drug in this family was put on the market 20 years ago, it was a radical change in the treatment of type 2 diabetics, who generally in 90% of cases have associated obesity. These drugs were a game-changer, because unlike the previous ones, they improved diabetic control and also helped with weight loss."

In this sense, Vázquez does not hesitate to describe them, like the other experts consulted, as "a family of super-effective, super-potent drugs on which there have been a large number of long-term studies on their efficacy and activity".

Tinahones explains that "Ozempic was marketed for the treatment of diabetes and the drug that has been approved for use in obese people is Wegovy, which is the same as Ozempic, but the maximum dose is 2.4 mg, while Ozempic is 1 mg the maximum dose of semaglutide."

Its use in Spain is explained by González: "Ozempic is not going to have an obesity indication. The same molecule, semaglutide, at a dose of 2.4 mg, whose trade name is Wegovi, is the one that is indicated for obesity. Last August, the Ministry of Health released the therapeutic positioning for obesity."

Morales and Vázquez point out that the revolution is not over yet. Since obesity is a disease that involves the whole body and its patients have other alterations, the use of this new generation of drugs will also bring other benefits to address them. "They are very safe drugs that have also been shown to be cardioprotective and renoprotective. The most frequent side effects are limited to symptoms of the digestive system, which are greatly minimized by escalating the doses," says Vazquez.

Antidiabetic drugs. Drugs

Beyond the management of type 2 diabetes, these have been a before and after in the treatment of obesity, "with results equivalent to surgical interventions, thus avoiding the need for bariatric surgery and the risks involved in going under the knife," says Morales, who is one of the main recruiters in Spain of patients in the trials that NovoNordisk and Lilly have been conducting. the labs behind the main molecules.

"Until now, we had drugs that produced discrete weight losses, but this therapeutic class manages to cause subjects to lose weight on average more than 15% of their body weight, which is clinically very significant," says Tinahones.

The CIBEROBN researcher offers the explanation that contextualizes what is happening now in the body: "Probably these signals that we had in our intestine not to eat more when we have taken an adequate amount, must have been downregulated during the evolution of hominids due to the difficulty of obtaining food and that regulation at this time of indiscriminate access to food is like an evolutionary error that in a certain way they come to correct these drugs."

Morales endorses a conclusion recently published in a Nature Medicine review on these molecules: "With great power comes great responsibility." The phrase, famous for other reasons, reflects the sentiment of the medical community: "We don't need just one pill, but a national plan that addresses prevention and goes to the source of obesity."

  • Diabetes
  • Obesity